Author: Nancy Meredith
FDA Grants Orphan Designation to Investigational Mesothelioma Drug
Boehringer Ingelheim announced in December that the U.S. Food and Drug Administration has granted orphan drug designation to its investigational cancer drug nintedanib for the treatment of mesothelioma.
Malignant pleural mesothelioma, a rare cancer caused by exposure to asbestos, is one of the nearly 7,000 diseases designated as rare, or “orphan,” in the United States. An orphan disease status is assigned to a disease or disorder if it affects fewer than 200,000 Americans at any given time. Mesothelioma is diagnosed in close to 3,000 Americans each year, and nearly the same number die from the asbestos-caused disease. There is no cure for the cancer.
The FDA notes that the Orphan Drug Designation program provides orphan status to drugs and biologics which are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases or disorders, or that affect more than 200,000 persons but the companies are not expected to recover the costs of developing and marketing a treatment drug.
According to Boehringer Ingelheim, the maker of nintedanib, also known as BIBF 1120, the drug is an oral triple angiokinase inhibitor which simultaneously inhibits vascular endothelial growth factor receptors (VEGFR 1-3), platelet-derived growth factor receptors (PDGFR) and fibroblast growth factor receptors (FGFR 1-3) signaling pathways. These three different angiokinase receptors play an important role in blood vessel formation and in tumor growth and metastases.
Nintedanib “has shown promise as a potential treatment for malignant pleural mesothelioma in clinical trials to-date, and this designation is a validating milestone in its development,” said Martina Flammer, M.D., Vice President, Clinical Development & Medical Affairs Specialty Care, Boehringer Ingelheim in a Dec. 14 press release from Boehringer Ingelheim. “We are proud to receive this designation for nintedanib from the FDA, resulting from our ongoing commitment to researching potential treatment options for rare cancers such as mesothelioma.”
The FDA granted designation based on the positive results from the ongoing Phase II/III LUME-Meso trial. Boehringer reports LUME-Meso is an international trial evaluating the efficacy and safety profile of nintedanib plus chemotherapy (pemetrexed/cisplatin) followed by nintedanib, versus placebo plus chemotherapy (pemetrexed/cisplatin) followed by placebo, in patients with unresectable malignant pleural mesothelioma.
“We are very encouraged by these recent data; the [clinical trial] results have led to an extension of the study into a Phase III confirmatory trial that is now underway and will provide further insight into the potential of nintedanib for patients with MPM [malignant pleural mesothelioma],” said lead investigator, Professor Giorgio V. Scagliotti, University of Torino, Chair of the Department of Oncology, Italy, at the 17th IASLC World Conference on Lung Cancer in Vienna.
Patients are currently being recruited worldwide for the trial. To find out more, see ClinicalTrials.gov.
Sources:
- ClinicalTrials.gov
https://clinicaltrials.gov/ct2/results?term=%22malignant+mesothelioma%22&recr=Open&pg=1 - Boehringer Ingelheim
https://www.boehringer-ingelheim.us/press-release/nintedanib-granted-orphan-drug-designation-treatment-mesothelioma - 17th IASLC World Conference on Lung Cancer
https://www.boehringer-ingelheim.us/press-release/clinically-meaningful-data-oral-nintedanib-mesothelioma-presented-world-conference
UK Researchers Identify Gene That May Limit Metastasis in Mesothelioma
Previous studies report that metastasis is the cause of nearly 90 percent of cancer deaths, but it remains poorly understood. Once cells mutate and spread to distant regions of the body the cancer becomes difficult, and in the case of pleural mesothelioma, impossible, to eradicate. Getting a handle on the spread of cancer is critical for increasing survival. Now, researchers report they have found a gene that can reduce metastasis by three-fourths.
Using mice models, researchers from the Wellcome Trust Sanger Institute of the UK identified 23 genes that either increased or decreased the spread of cancer cells to the lungs. They also found that these genes impacted the immune system, the body’s natural defense mechanism for fighting cancer. They homed in on the Spns2 gene and found that when the gene was removed, the largest change occurred resulting in a reduction of nearly four times in the spread of tumors to the lungs. The researchers reported that the effect of this gene on colon, lung and breast cancers also resulted in reduced metastasis.
“Loss of the Spns2 gene causes the greatest reduction in the formation of tumour colonies and represents a novel therapeutic target,” said Dr. David Adams from the Wellcome Trust Sanger Institute, in a Jan. 11 press release. “Drugs that target this could help reduce or prevent the spread of tumours through the body.”
Stopping tumor growth and preventing metastasis is especially critical for increasing survival in mesothelioma and lung cancer patients. Mesothelioma is one of the most aggressive cancers, and one of the reasons is due to the ability of asbestos fibers to become embedded in the lining of the lungs and to fester for years, even decades, before any symptoms develop. Once mesothelioma is diagnosed, it is typically in an advanced stage where treatment is moot.
This research, however, led the researchers to better understand the Spns2 gene’s impact on the immune system and in tumor spread. This combination brings hope to many in the cancer community that an effective treatment could deliver a one-two punch by waking up the immune system and halting metastasis.
Expert Insight
Dr Justine Alford, Cancer Research UK
“Cancer that has spread is tough to treat, so research such as this is vital in the search for ways to tackle this process.”
These findings suggest another unique cancer characteristic to be considered when personalizing care for lung cancer and mesothelioma patients. Targeted therapy improves the prognosis in people suffering from mesothelioma and other cancers.
“This work supports the emerging area of immunotherapy, where the bodies’ own immune system is harnessed to fight cancer,” said Dr. Anneliese Speak of the Sanger Institute. “Investigation of further targets in the Spns2 pathway, or other targets identified in this study could help develop potential therapies.”
Older Patients Burdened by Mesothelioma and Lung Cancer Treatments
The American Cancer Society reports that lung cancer mainly occurs in older people, with about two out of three lung cancer patients aged 65 or older. The average age at the time of diagnosis is about 70. Pleural mesothelioma, a cancer caused by exposure to asbestos, produces tumors that grow uncontrollably in the lining of the lung and is equally as aggressive and difficult to treat as lung cancer. About three out of four people with mesothelioma are older than 65 years. Now, researchers report that these older patients “face a significant treatment burden” when diagnosed with cancer.
According to a Jan. 10 article in Medical News Today, this older population of patients may face spending one-third of their time interacting with medical teams for the 60 days following surgery or radiation. Previous research has shown that nearly half of older cancer patients have medical problems that also need to be addressed such as reduced physical functioning, nutritional deficiencies, fatigue and depression. Pointing to all of these issues, researchers from Yale found after treatment for cancer, older patients saw an average of 20 different physicians and took 12 different medications.
“To our knowledge, this is the first study to characterize treatment burden for early-stage lung cancer patients in terms of touches with the healthcare system, including emergency department visits, hospital-based follow-up care, number of physicians, and outpatient visits,” said first author Carolyn Presley, M.D., instructor at Yale Cancer Center and a Robert Wood Johnson Clinical Scholar at Yale School of Medicine.
This news may come as no surprise to many in the mesothelioma community who have battled pleural mesothelioma themselves or who stood by their loved one as they underwent treatment. Battling any disease for the older population is difficult, but dealing with a painful, incurable cancer can be extremely challenging. Treatment for mesothelioma is often a complex regimen including surgery, chemotherapy and radiation. These treatments also come with a set of side effects that can lead to more medical challenges in an older patient.
“These findings highlight a need to improve cancer care coordination. It’s also a call for providers to think about the burden we might be placing on patients,” said Carolyn Presley, M.D.
While the average survival time of mesothelioma patients typically varies from 4 – 18 months after diagnosis, many factors determine the life expectancy. Factors include type and stage of mesothelioma, treatment plan, whether the patient has ever smoked, the lifestyle, diet and fitness level of the patient, as well as age, sex and family traits.
Read the full study in the January issue of Journal of Oncology Practice.
Vitamin C May Kill Mesothelioma Cancer Cells
Research has shown that the antioxidant effects of vitamin E could protect healthy cells from the damaging effects of free radicals helping to keep cancer at bay. Vitamin C has also been studied for its impact on cancer with research showing the vitamin can limit cancer cell growth in mesothelioma, colon cancer, and prostate cancers, among others. Now, researchers report that high-dose, intravenous delivery of Vitamin C in lung cancer patients could kill the cancer cells.
According to a Jan. 9 article in the Science Daily, researchers from the University of Iowa believe that many attempts at using Vitamin C in cancer care have failed because delivery has been oral. However, in their study, high doses of Vitamin C were given intravenously. This method of delivery, as opposed to oral delivery, results in very high blood levels of vitamin C – 100-500 times higher – by bypassing normal ingestion and excretion processes. According to the researchers, “It is this super-high concentration in the blood that is crucial to vitamin C’s ability to attack cancer cells.” At this high level, cancer cells are killed, but the other cells are left intact.
The researchers used a mouse study to understand the underlying biological processes of the high-dosage vitamin C and cancer.
The team found that when vitamin C breaks down it generates hydrogen peroxide that can lead to tissue and DNA damage. Normal cells can process, or remove, the peroxide, but cancerous cells cannot making the cancer cells more prone to death when they are hit with high doses of vitamin C. The researchers determined that the healthy cells used an enzyme called catalase to decompose the vitamin and remove the hydrogen peroxide keeping the cells healthy and undamaged. Not so for the cancerous cells, they had lower amounts of catalase, thus, making them more susceptible to death with high amounts of vitamin C.
“Our results suggest that cancers with low levels of catalase are likely to be the most responsive to high-dose vitamin C therapy, whereas cancers with relatively high levels of catalase may be the least responsive,” said Garry Buettner, a professor of radiation oncology and a member of Holden Comprehensive Cancer Center at the University of Iowa.
A future goal of the research is to develop methods to measure catalase levels in tumors, said Buettner.
Pleural mesothelioma is a serious and rare cancer affecting the lining of the lungs in individuals who were exposed to asbestos fibers in the past. Like lung cancer, mesothelioma is highly aggressive and is resistant to many standard cancer treatments, making breakthroughs of effective treatments critical to the mesothelioma community. Currently there is no known cure for mesothelioma, and the average survival time varies from 4 – 18 months after diagnosis.
The treatments for lung cancer and pleural mesothelioma are very similar bringing hope to the mesothelioma community when success is seen in studies in the lung cancer community. Continued research for bringing improved treatment options to mesothelioma patients can increase survival and improve their quality of life.
Read the full study in the Dec. 2016 issue of Redox Biology.
Protein Overexpression Points to Pleural Mesothelioma
Proteins are essential for normal cell structure and function and can support critical biological processes such as enzymes for metabolism and antibodies for immune defense. However, when a protein becomes over-expressed it can lead to illness and disease. Now, researchers report that high levels of the protein FGF18 can point to pleural mesothelioma.
Researchers from the Medical University of Vienna, Austria, joined by scientists from Switzerland and Australia, reported at the 17th Annual World Conference on Lung Cancer in Austria in Dec. that the Fibroblast Growth Factor 18 (FGF18) pointed to malignant pleural mesothelioma when overexpressed and could be used as both a diagnostic and prognostic marker.
The researchers measured levels of FGF18 in 107 patients with pleural mesothelioma and 49 healthy volunteers. They found that the plasma levels of FGF18 was “significantly elevated” in the mesothelioma patients. In addition, they found that the mesothelioma patients with FGF18 levels below the median had “significantly longer overall survival” than those patients with high FGF18 levels.
“The identification of novel biomarkers is urgently needed in order to identify patients with a better prognosis and to support personalized therapeutic decisions,” noted the authors. “In our previously published study, we were able to show that fibroblast growth factor 18 (FGF18) is overexpressed in MPM [malignant pleural mesothelioma] tissue specimens and cell models.”
FGF18, according to the GeneCards website, plays an important role in the regulation of cell proliferation. The protein is in a variety of biological processes including embryonic development, cell growth, and tumor growth and invasion.
Pleural mesothelioma is a cancer that develops decades after exposure to the mineral asbestos. The microscopic fibers are inhaled and become embedded in the lining of the lungs where they eventually become inflamed and can lead to cancer. Nearly 3,000 Americans are diagnosed with the terminal cancer each year.
Continued research into finding the biomarkers that can lead to mesothelioma and effective treatments for those biomarkers is critical to increase survival for patients. The prognosis for mesothelioma patients is often less than 18 months.
To find out more about this study see the January 2017 issue of the Journal of Thoracic Oncology.
Sources:
- 17th Annual World Conference on Lung Cancer in Austria
http://www.cancertherapyadvisor.com/iaslc-2016/malignant-pleural-mesothelioma-new-biomarker-identified/article/576850/ - Journal of Thoracic Oncology
http://journals.lww.com/jto/Pages/default.aspx?PAPNotFound=true - GeneCards website
http://www.genecards.org/cgi-bin/carddisp.pl?gene=FGF18
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